Nearly 90 percent of patients with schizophrenia smoke cigarettes compared to less than 25 percent of the general U.S. adult population. Compounded by the problem that patients with schizophrenia are less likely to receive adequate routine and preventative medical care, heavy smoking represents a significant and neglected public health problem for people with schizophrenia. Moreover, with conventional approaches, patients with psychiatric illness are much less likely to quit than smokers without psychiatric illness. Efforts at smoking cessation therapy in schizophrenia have received little attention in the literature until very recently. Nicotine replacement therapy (NRT) has been only modestly successful for smoking cessation in patients with schizophrenia, with reported cessation rates of 13 percent at 6 months, roughly equivalent to placebo quit rates in non-psychiatric patients. In patients without current psychiatric illness sustained release (SR) bupropion has been shown to be superior to placebo and has been found to be effective for smoking cessation in our preliminary open trial in patients with schizophrenia. In the proposed study, 70 subjects with schizophrenia who smoke greater than 10 cigarettes per day and wish to stop smoking will be randomized, in double blind fashion, to receive either SR bupropion 150 mg/d or placebo for twelve weeks, combined with nine week cognitive behavioral Quit Smoking Group therapy. The primary outcome measure is 7-day point prevalence tobacco abstinence at the end of the 3 month treatment phase which is biochemically confirmed. Secondary outcome measures are biochemically confirmed 7-day point prevalence tobacco abstinence at 6 months, sustained tobacco abstinence during the 3 month treatment phase and during the subsequent 3 month follow-up period; change in psychiatric symptoms and side effects of medications, especially positive and negative symptoms of schizophrenia and symptoms of depression. Health related quality of life will be assessed at baseline, 3 and 6 months and cognitive functioning will be assessed at baseline and 3 months.